Abstract
Whether microRNAs (miRNAs) from plasma exosomes might be dysregulated in patients with depression, especially treatment-resistant depression (TRD), remains unclear, based on study of which novel biomarkers and therapeutic targets could be discovered. To this end, a small sample study was performed by isolation of plasma exosomes from patients with TRD diagnosed by Hamilton scale. In this study, 4 peripheral plasma samples from patients with TRD and 4 healthy controls were collected for extraction of plasma exosomes. Exosomal miRNAs were analyzed by miRNA sequencing, followed by image collection, expression difference analysis, target gene GO enrichment analysis, and KEGG pathway enrichment analysis. Compared with the healthy controls, 2 miRNAs in the plasma exosomes of patients with TRD showed significant differences in expression, among which has-miR-335-5p were significantly upregulated and has-miR-1292-3p were significantly downregulated. Go and KEGG analysis showed that dysregulated miRNAs affect postsynaptic density and axonogenesis as well as the signaling pathway of axon formation and cell growths. The identification of these miRNAs and their target genes may provide novel biomarkers for improving diagnosis accuracy and treatment effectiveness of TRD.
Highlights
Depression has been a common mental illness and major public health problem
Exosomes released by the invagination of intracellular lysosomal micro-particle in the central nervous system (CNS) may play an active role in the occurrence or development of diseases in the CNS such as Alzheimer’s disease (AD), Parkinson’s disease (PD), prion disease, multiple sclerosis (MS), schizophrenia (SCZ), and brain tumors [9]
Bone marrow mesenchymal stem cell-derived exosomes upregulated miR-26a to boost hippocampal neuron proliferation and suppressed apoptosis in depressed rats [21], and NK cell-derived exosomes could carry miR-207and alleviate depressionlike symptoms in mice [22]. These results indicate that exosomes are involved in the occurrence and development of depression and other mental disorders
Summary
Depression has been a common mental illness and major public health problem. Its core symptoms are characterized by low mood and anhedonia. Li et al Human Genomics (2021) 15:55 research on biomarkers of depression has become a new hotspot. Exosomes are extracellular vesicles with a lipid bilayer and a diameter of 40–200nm. They are widely distributed in the blood, cerebrospinal fluid (CSF), urine, and other body fluids. Many cells in an organism, including neurons, can secrete exosomes [7]. The bilayer membrane structure of exosomes allows them to bind to the cell membrane and readily cross the blood-brain barrier (BBB) to regulate the function of the nervous system [8]. There are various biologically active molecules, including lipids, proteins, and small RNA in exosomes, which could be transported to nearby or distant cells. A large number of studies have shown that exosomes play an important role in the communication of the CNS, neural regeneration, synaptic plasticity, and neuroinflammation [10,11,12]
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